چکیده انگلیسی

In the U.S. and worldwide anabolic/androgenic steroid use remains high in the adolescent population. This is concerning given that anabolic/androgenic steroid use is associated with a higher incidence of aggressive behavior during exposure and anxiety during withdrawal. This study uses pubertal Syrian hamsters (Mesocricetus auratus) to investigate the hypothesis that an inverse behavioral relationship exists between anabolic/androgenic steroid-induced aggression and anxiety across adolescent exposure and withdrawal. In the first experiment, we examined aggression and anxiety during adolescent anabolic/androgenic steroid exposure and withdrawal. Adolescent anabolic/androgenic steroid administration produced significant increases in aggression and decreases in anxiety during the exposure period followed by significant decreases in aggression and increases in anxiety during anabolic/androgenic steroid withdrawal. In a second experiment, anabolic/androgenic steroid exposed animals were separated into groups based on their aggressive response during the exposure period and then tested for anxiety during exposure and then for both aggression and anxiety during withdrawal. Data were analyzed using a within-subjects repeated measures predictive analysis. Linear regression analysis revealed that the difference in aggressive responding between the anabolic/androgenic steroid exposure and withdrawal periods was a significant predictor of differences in anxiety for both days of testing. Moreover, the combined data suggest that the decrease in aggressive behavior from exposure to withdrawal predicts an increase in anxiety-like responding within these same animals during this time span. Together these findings indicate that early anabolic/androgenic steroid exposure has potent aggression- and anxiety-eliciting effects and that these behavioral changes occur alongside a predictive relationship that exists between these two behaviors over time.

نتیجه گیری انگلیسی

Aggression and anxiety during adolescent AAS exposure and withdrawal
Aggressive behavior
As reported in a number of our prior studies (see Melloni and Ricci, 2010 for a review), adolescent AAS administration results in a significant increase in offensive aggression during the adolescent exposure period (i.e., on P57) compared to SO-treated control animals (t(44) = 5.29, p < 0.001) ( Fig. 1). During adolescent exposure, AAS-treated animals exhibited a greater than six-fold increase in the number of attacks compared to SO-treated controls. Also, consistent with our previous data ( Carrillo et al., 2011, Grimes and Melloni, 2006, Grimes et al., 2006 and Ricci et al., 2012), behavioral data from the current study showed that the aggression-stimulating effects of adolescent AAS exposure were no longer present at 3 weeks of AAS withdrawal (i.e., on P77), i.e., a time at which AAS-treated animals were no longer aggressive and displayed a non-aggressive phenotype identical to SO-treated control animals (t(43) = 1.98, p > 0.1). Further, within-treatment group comparisons revealed that AAS-treated animals displayed a significantly lower level of aggression during withdrawal from adolescent AAS exposure (i.e., on P77) as compared to that observed during the AAS exposure period (i.e., on P57) (t(37) = 2.471, p < 0.05) ( Fig. 1, upper inset). During withdrawal from adolescent AAS exposure (i.e., on P77), residents executed nearly 3-fold fewer attacks onto intruders placed in their home cage compared to animals tested during adolescent AAS exposure. Conversely, however, no significant difference was observed in aggression between the exposure and withdrawal periods in SO-treated control animals. In this case, SO-treated animals directed a nearly identical number of attacks onto intruders (i.e., 2.6 ± 0.1.3 attacks) during the withdrawal period (i.e., on P77) as compared to the exposure period (i.e., 2.67 ± 0.97 attacks on P57) (t(16) = 0.076, p > 0.1).
Full-size image (42 K)
Fig. 1.
Adolescent AAS exposure alters aggression and anxiety during adolescent AAS exposure and withdrawal. Top Graphs. The number of attacks of control- (SO; white bars) and AAS- (black bars) treated hamsters in a resident/intruder (R/I) test during adolescent exposure (i.e., on P57) and withdrawal (i.e., on P77). Top Inset. The number of attacks of AAS-treated hamsters during adolescent AAS exposure (i.e., on P57, striped bars) and withdrawal (i.e., on P77, black bars). Bottom Graphs. The duration of time control- (SO; white bars) and AAS- (black bars) treated hamsters spent in the open arm of the elevated plus maze (EPM) during adolescent exposure (i.e., on P57) and withdrawal (i.e., on P77). Bottom Inset. The duration of time spent in the open arm of the EPM of AAS-treated hamsters during adolescent AAS exposure (i.e., on P57, striped bars) and withdrawal (i.e., on P77, black bars). Bars denote SEM; *p < 0.05, **p < 0.01, ***p < 0.001.
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Anxiety
Adolescent AAS-treated animals displayed a significantly lower level of anxiety-like behavior during adolescent AAS exposure (i.e., on P57) compared to SO-treated control animals as measured by the duration of time spent in the open arms of the EPM (t(40) = 2.22, p < 0.05) ( Fig. 1). Indeed, during adolescent AAS exposure, AAS-treated animals spent significantly more time (> 30% more time) in the open arms of the EPM compared to SO-treated control animals. However, behavioral data from the current study showed that the anxiolytic effects of adolescent AAS exposure were no longer present at 3 weeks of AAS withdrawal (i.e., on P77). Rather, consistent with our recent findings ( Ricci et al., 2012), during withdrawal from adolescent AAS administration (i.e., on P77), AAS-treated animals displayed a higher level of anxiety-like responding in the EPM compared to SO-treated controls. Specifically, during withdrawal from adolescent AAS exposure, AAS-treated animals spent significantly less time (< 20% less time) in the open arms of the EPM compared to SO-treated control animals (t(45) = 2.05, p < 0.05) ( Fig. 1). Within treatment group comparisons revealed that AAS-treated animals displayed a significantly higher level of anxiety-like behavior in the EPM test during withdrawal from adolescent AAS exposure (i.e., on P77) as compared to that observed during AAS exposure (i.e., on P57) ( Fig. 1, lower inset). During withdrawal from adolescent AAS exposure, the animals spent significantly less time in the open arms of the EPM compared to the duration of time spent in the open arms of the EPM during the AAS exposure period (t(41) = 4.65, p < 0.001). During AAS withdrawal, the animals spent less than 50% of the time in the open arms of the EPM compared to the animals tested during adolescent AAS exposure. Conversely, however, no significant difference was observed in anxiety-like behavior between the exposure and withdrawal periods in SO-treated control animals. In this case, SO-treated animals spent an average of 81.52 ± 9.8 s in the open arms of the EPM during the withdrawal period (i.e., on P77) as compared to 80.79 ± 4.3 s in the open arms of the EPM during the exposure period (i.e., on P57) (t(19) = 0.081, p > 0.1).
Adolescent AAS-induced aggression: Quantitative separation of responders
Based on our hypothesis that aggression and anxiety are inversely related in adolescent AAS-treated animals, the animals were divided into adolescent AAS-induced No/Low (NL), Species Normative (SN) and Excessive (E) responder groups as defined by their aggression level displayed during the adolescent AAS exposure period (i.e., on P57) as compared to SO-treated littermates.